The major objectives are to study the chemistry and metabolism of glycosphingolipids, particularly the gangliosides, in normal and pathological brains and spinal cords. We will engage in large scale isolation of gangliosides from normal brains employing improved column chromatographic techniques; and in the elucidations of new ganglioside structures and biosynthetic pathways. We will also examine the gangliosides in myelin and oligodendroglia in order to study the relationship between myelin and oligodendroglia. This will be aided by focusing on a specific ganglioside, sialosylgalactosylceramide, in these two compartments. In addition we will study the developmental aspects of gangliosides in the process of myelination. A major effort will be devoted to the characterization of the chemical composition of normal and multiple sclerosis spinal cord. Emphasis will be placed on the glycosphingolipids in spinal cord, cord myelin, and MS plaques in addition to the proteins in cord myelin. We will also study the gangliosides in the brains of an animal model for slow virus disease, scrapie. This work will provide us with some important biochemical information on the pathogenesis of slow virus diseases; and perhaps will give some clue as to the etiology of multiple sclerosis.